Section Summary

The stress response is a non-specific physiological reaction to any event (stressor) that takes an organism out of homeostatic range. It is necessary for survival and to adapt to challenges. Stressors are classified by type, severity, and duration. The stress response follows an inverted-U pattern: too little or too much stress is deleterious to behavioral performance but there is an optimal level that is beneficial. Research on stress seeks to understand the mechanisms underlying both pathological and salutary effects of stress in humans and is carried out using humans and animal models.

The stress response depends on multiple interconnected systems working on different timescales. The fast neural response is mediated by the SNS via the sympatho-neural system and sympatho-adrenomedullary system. The slower neuroendocrine response depends upon the HPA axis and is important for the long-term effects of the stress response as well as various other bodily functions. Activation of the HPA axis involves serial activation of the hypothalamus, pituitary gland, and adrenal gland to produce stress hormones. This in turn, produces changes in glucocorticoid levels with effects throughout the body. Termination of the stress response is not a clear-cut event, but vagal stimulation (through deep breathing) can engage the PNS and inhibit the SNS and help to restore homeostasis. Cortisol levels return more slowly to baseline with help from negative feedback mechanisms.

The brain orchestrates the body´s response to stress and stress, in turn, has major effects on brain circuitry, resulting in long-lasting changes in structure, function, and behavior. Major brain regions that are affected by stress and mediate behavioral responses include the prefrontal cortex, amygdala, hippocampus, and hypothalamus. These brain regions express stress hormone receptors and thus are directly stimulated by stress hormones. At the same time, they also receive signals via connections to other brain regions.

Numerous factors (genetic, epigenetic, life history, biological sex, emotional and physiological state, as well as the characteristics of the specific stressor) are involved in determining interindividual variability in response to stress. Additionally, the perception, appraisal, and predictability/controllability of stressors can profoundly affect stress reactivity and stress outcomes. Not all stress is bad, however, and some types of stress can have salutary effects on brain function. Stress can also promote social affiliation which is associated with increased health and life expectancy.

Repeated or prolonged stress can lead to allostatic over(load) resulting in stress-related pathologies like mood, anxiety, cognitive, memory, impulse control and substance abuse disorders. Exposure to traumatic stress can lead to development of PTSD. Additionally, chronic stress can drive microglial priming and neuroinflammation which exacerbates mood and cognitive disorders and contributes to neurodegeneration.